Full-automatic freezing rapid immunohistochemical staining equipment

Abstract

The utility model provides full-automatic freezing rapid immunohistochemical staining equipment which comprises a control module, a pipetting arm, a reagent washing and mixing module, a movable nozzle, a container bin module, a slide staining device and a cleaning system, the pipetting arm is a three-dimensional pipetting arm with an X-axis, Y-axis and Z-axis three-direction moving function, and the reagent washing and mixing module comprises a reagent assembly, a mixing station and a cleaning pool. The container bin module comprises a waste liquid bin, a cleaning liquid bin and a purified water bin, the cleaning liquid bin and the purified water bin are connected to the cleaning system through pipelines, and the cleaning system is connected to a liquid opening of the movable nozzle and the cleaning pool and finally flows back to the waste liquid bin; the cleaning system is further connected to an air port of the movable nozzle through a pipeline, and the control module controls the slide dyeing device to move in or out of the equipment. The problems that in the prior art, immunohistochemical staining is long in time, small in equipment flux and large in equipment size are solved.

Description

TECHNICAL FIELD

[0001] The utility model belongs to the technical field of immunohistochemical dyeing, and particularly relates to a full-automatic frozen rapid immunohistochemical dyeing equipment. BACKGROUND

[0002] Immunohistochemistry is a technology for locating, qualitatively and relatively quantitatively studying antigens in tissues and cells by using the basic principle of immunology, i.e. antigen-antibody reaction, and making the color developing agent of the labeled antibody develop color through chemical reaction.

[0003] The immunohistochemical reaction is long in time and complicated in operation, and in the existing immunohistochemical detection, several sample slides with known properties are often prepared as controls, and are placed in an immunohistochemical instrument together with the sample slides to be detected for experiment, but since the processing is not performed on the same slide, it is not a complete control in the whole process. With the innovation of the technology in the field, in order to improve the immunohistochemical quality control effect, a specified quality control sample reagent needs to be added to the blank area around the sample as a complete control. The reagent needs to form a spot meeting the requirements, and cannot spread too much to contaminate the sample to be detected. This pre-processing process has certain requirements for operation accuracy, and currently, it needs to be completed by manual operation, which requires a lot of time and effort, and lacks corresponding automatic equipment.

[0004] The difficulty in realizing automatic operation in the field at present lies in that: in order to realize high-throughput processing, a large number of slides are used in one-time experiment, and a large number of slide racks are also needed to hold the slides. The existing immunohistochemical instrument adopts a scheme of placing the slides and slide racks flat, and when high-throughput experiment needs to be met, a large area is occupied by the placement of the slides, which leads to a large area occupied by the equipment, and at the same time, the running range of the sample adding mechanical arm for sample adding operation is increased, which reduces the work efficiency and also increases the difficulty of automatic control. UTILITY MODEL CONTENTS

[0005] In order to solve the above problems existing in the prior art, the present application provides a full-automatic frozen rapid immunohistochemical dyeing equipment to solve the above technical defect problems.

[0006] According to a first aspect of this utility model, a fully automated frozen rapid immunohistochemical staining device is proposed, comprising a control module, a pipette arm, a reagent washing and mixing module, a movable nozzle, a container module, a slide staining device, and a cleaning system. The pipette arm is a three-dimensional pipette arm with three-way movement functions in the X, Y, and Z axes. The reagent washing and mixing module includes reagent components, a mixing station, and a cleaning tank. The container module includes a waste liquid tank, a washing liquid tank, and a purified water tank. The washing liquid tank and the purified water tank are connected to the cleaning system via pipelines. The cleaning system is then connected to the liquid outlet of the movable nozzle and the cleaning tank, respectively, and finally flows back to the waste liquid tank. The cleaning system is also connected to the air outlet of the movable nozzle via pipelines. The control module controls the movement of the slide staining device into or out of the device. Through this structural design, a fixed liquid flow path is established from the washing liquid tank and the purified water tank through pipelines to the cleaning system, then through the liquid outlet of the movable nozzle and the cleaning tank, and finally back to the waste liquid tank. A gas diffusion path is also established from the cleaning system through the air outlet of the movable nozzle, which facilitates the automated staining process of the device.

[0007] In a specific embodiment, the pipetting arm includes a symmetrically arranged left pipetting arm and a right pipetting arm, and the left and right pipetting arms operate independently. This structural arrangement helps improve the structural stability of the equipment and also improves its working efficiency.

[0008] In a specific embodiment, the slide staining device has multiple independent channels, each capable of loading multiple slides simultaneously. This structural design allows the device to process multiple slides at the same time, which helps to shorten the processing time for batches of slides and achieve high throughput.

[0009] In a specific embodiment, the slide staining device is configured with 8 groups, each group corresponding to an independent channel. This structural arrangement allows the device to process 8 groups of slides in parallel within the same time period, significantly improving the device's working efficiency.

[0010] In a specific embodiment, the control module also controls the movement of the pipette arm and the movable nozzle. This structural design allows the pipette arm and the movable nozzle to move to a designated position or range according to the pre-set process in the device, which facilitates the automation of the staining process.

[0011] In a specific embodiment, the control module controls the movable nozzle to move along the X-axis to above the slide in the slide staining apparatus. The cleaning system draws cleaning fluid from the cleaning fluid tank and sprays it out through the nozzle's outlet. In this configuration, the movable nozzle moves linearly along the X-axis, rather than along a complex multi-axis path. Combined with the fixed position of the slide staining apparatus, this facilitates the achievement of the shortest path coverage, reduces the time for a single cleaning cycle, and improves the equipment's efficiency.

[0012] In specific embodiments, when the air port of the mobile nozzle blows air, the control module controls the slide staining device to move in the negative direction of the Y axis. In this structure, the slide staining device moves towards the mobile nozzle, which is beneficial to dry the excess liquid on the slide.

[0013] In specific embodiments, the pipette arm is provided with a steel needle, which is used to suck reagents in the reagent assembly. Through this structure, the reagent can be accurately dispensed.

[0014] In specific embodiments, when in working condition, the control module controls the pipette arm to move above the reagent assembly, the steel needle to extract the reagent in the reagent assembly, and the pipette arm to move above the slide staining device. Through this structure, the movement of the pipette arm is accurately controlled when in working condition, the steel needle is accurately positioned, which is beneficial to accurately complete the work of the steel needle droplet and improve the automation of the equipment.

[0015] In specific embodiments, when out of working condition, the steel needle moves to the inside of the cleaning pool, the cleaning system starts, and the steel needle resets to the original point. Through this structure, the steps of cleaning the inner and outer walls of the steel needle are automatically completed under the control of the control module, which is beneficial to reduce the risk of reagent cross contamination; the steel needle is reset, which is beneficial to the next droplet step of the steel needle.

[0016] Compared with the prior art, the beneficial results of the present application are as follows:

[0017] 1. The equipment adopts a double pipette arm scheme, which can quickly complete intraoperative frozen immunohistochemical independent staining within 10 minutes, and the staining time is short.

[0018] 2. The equipment has 8 independent channels and can simultaneously stain eight slides, with large throughput.

[0019] 3. The equipment is fully automatic and has small floor area, which is beneficial to laboratory popularization. BRIEF DESCRIPTION OF DRAWINGS

[0020] The accompanying drawings are included to provide a further understanding of embodiments and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments and serve the purpose of explaining the principles of the present application. Other embodiments and many of the intended advantages of the embodiments will be readily appreciated as they become better understood by reference to the following detailed description. The elements of the drawings are not necessarily to scale relative to each other. Like reference numbers designate corresponding similar parts.

[0021] Figure 1 is a front side structure schematic diagram of a full-automatic frozen rapid immunohistochemical staining equipment according to an embodiment of the present application;

[0022] Figure 2It is the left view of the full-automatic frozen rapid immunohistochemical staining equipment according to an embodiment of the utility model,

[0023] Figure 3 It is the rear side structure schematic view of the full-automatic frozen rapid immunohistochemical staining equipment according to an embodiment of the utility model,

[0024] Figure 4 It is the structure schematic view of reagent washing and mixing module according to an embodiment of the utility model,

[0025] Figure 5 It is the schematic view of container warehouse module according to an embodiment of the utility model.

[0026] The meanings of various reference numerals in the drawings are as follows: 1-control module, 2-right pipetting arm, 3-left pipetting arm, 4-reagent washing and mixing module, 5-mobile nozzle, 6-slice staining device, 7-container warehouse module, 8-cleaning system, 9-steel needle, 10-supporting frame, 401-reagent assembly, 402-mixing station, 403-cleaning pool, 701-waste liquid warehouse, 702-cleaning liquid warehouse, 703-purified water warehouse, 801-pump assembly, 802-valve assembly, 803-pipeline assembly. DETAILED DESCRIPTION

[0027] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof, and in which are shown by way of illustration illustrative embodiments in which the application can be practiced. For purposes of explanation and illustration, directional terms are used with reference to the orientation of the described figures. However, it is to be understood that the embodiments can be practiced in other orientations than those described and shown. The directional terms, such as "top," "bottom," "left," "right," "upper," "lower," and the like, are used to aid in describing the embodiments and are not limiting. It will be apparent to one of ordinary skill in the art that the embodiments can be practiced in other specific embodiments or in other ways without departing from the spirit and scope of the application. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the application is defined by the appended claims.

[0028] The utility model provides a kind of automatic frozen rapid immunohistochemical staining equipment, Figure 1 The front side structure schematic view of the automatic frozen rapid immunohistochemical staining equipment of one embodiment of the utility model is shown.As shown in the figure, Figure 1As shown, the device comprises a control module 1, a left pipetting arm 3, a right pipetting arm 2, a reagent washing and mixing module 4, a movable nozzle 5, a container warehouse module 7, a slide staining device 6 and a cleaning system 8. Among them, the left pipetting arm 3 and the right pipetting arm 2 are both three-dimensional pipetting arms with X, Y and Z axis three-dimensional movement function; the reagent washing and mixing module 4 comprises a reagent assembly 401, a mixing station 402 and a cleaning pool 403; the container warehouse module 7 comprises a waste liquid warehouse 701, a cleaning liquid warehouse 702 and a purified water warehouse 703. Among them, the left pipetting arm 3 and the right pipetting arm 2 are symmetrically arranged on both sides of the device, and the left pipetting arm 3 and the right pipetting arm 2 independently operate. Through the structure setting, it is beneficial to improve the structural stability of the device, and at the same time, it is beneficial to improve the working efficiency of the device.

[0029] In specific embodiments, the cleaning liquid warehouse 702 and the purified water warehouse 703 are connected to the cleaning system 8 through pipelines, the cleaning system 8 is connected to the liquid port of the movable nozzle 5 and the cleaning pool 403 respectively, and finally flows back to the waste liquid warehouse 701, forming a liquid path channel; the cleaning system 8 is also connected to the gas port of the movable nozzle 5 through the pipeline, forming a gas path channel. Through the structure setting of the fixed liquid path channel and the gas path channel, it is beneficial to realize the automatic operation of the device.

[0030] In specific embodiments, the slide staining device 6 is provided with 8 groups, and is provided with a plurality of independent channels for simultaneously carrying a plurality of slides, and each group of slide staining devices 6 corresponds to an independent channel. Through the structure setting, the device can process multiple slides in the same period, which is beneficial to shorten the time of processing batch slides of the device, realize high throughput of the device, and improve the working efficiency of the device. It can be understood that the slide staining device 6 here can also be 6 groups, 7 groups or other groups, and each group of slide staining devices 6 has the same working condition, and multiple groups are provided to improve the working efficiency of the device.

[0031] In specific embodiments, the left pipetting arm 3 and the right pipetting arm 2 are provided with a steel needle 9, which is used to suck the reagent in the reagent assembly. Through the structure setting, the precise distribution of the reagent can be realized.

[0032] In specific embodiments, the control module 1 controls the slide staining device 6 to move into or out of the device, and the control module 1 also controls the movement of the left pipetting arm 3, the right pipetting arm 2 and the movable nozzle 5. Through the structure setting, the slide staining device 6, the left pipetting arm 3, the right pipetting arm 2 and the movable nozzle 5 move to the specified position or range according to the process set in the device, which is beneficial to realize the automatic staining process of the device.

[0033] In specific embodiments, when the liquid port of the movable nozzle 5 sprays liquid, the control module 1 controls the movable nozzle 5 to move above the slide of the slide staining device 6 in the X-axis direction, and the cleaning system 8 draws the cleaning liquid in the cleaning liquid tank 702 and sprays it through the liquid port of the movable nozzle 5. In this structure, the movable nozzle 5 moves linearly along the X-axis rather than a complex multi-axis path, and cooperates with the fixed position of the slide staining device 6, which is beneficial to realize the shortest path coverage, shorten the single cleaning time, and improve the working efficiency of the equipment.

[0034] In specific embodiments, when the gas port of the movable nozzle 5 blows gas, the control module 1 controls the slide staining device 6 to move in the negative direction of the Y-axis. In this structure, the slide staining device 6 moves towards the movable nozzle 5, which is beneficial to dry the excess liquid on the slide.

[0035] In specific embodiments, when in the working state, the control module 1 controls the left pipette arm 3 and the right pipette arm 2 to move above the reagent assembly 401, the steel needle 9 draws the reagent in the reagent assembly 401, and moves above the slide staining device 6. Through this structure, the movement of the left pipette arm 3 and the right pipette arm 2 is accurately controlled when in the working state, the high-precision positioning of the steel needle 9 is realized, which is beneficial to accurately complete the liquid dropping work of the steel needle 9, and improve the automation degree of the equipment.

[0036] In specific embodiments, when the working state is separated, the steel needle 9 moves to the inside of the cleaning pool 403, the cleaning system 8 is started, and after cleaning, the steel needle 9 is reset to the original point. Through this structure, the steps of cleaning the inner and outer walls of the steel needle 9 are automatically completed under the control of the control module 1, which is beneficial to reduce the risk of reagent cross contamination; the steel needle is reset, which is beneficial to the next liquid dropping step of the steel needle.

[0037] Figure 2 A left view of the full-automatic frozen rapid immunohistochemical staining equipment is shown in one embodiment of the utility model. As shown in Figure 2 The steel needle 9 is connected to the left pipette arm 3, and when the equipment is in the working state, the left pipette arm 3 provides the movement of the steel needle 9 in the X, Y and Z-axis directions; when the equipment is separated from the working state, the steel needle 9 is reset and is in the left zero position. Among them, in the X-axis direction of the left zero position, the steel needle 9 is on the left side of the mixing station 402; in the Y-axis direction of the left zero position, the steel needle 9 is behind the reagent assembly 401; in the Z-axis direction of the left zero position, the steel needle 9 is above the reagent assembly 401. It can be understood that the other steel needle 9 is connected to the right pipette arm 2, and when the equipment is separated from the working state, the steel needle 9 is reset and is in the right zero position, and the right zero position and the above-mentioned left zero position are left-right symmetrical.

[0038] Figure 3The rear side structure schematic view of the full-automatic frozen rapid immunohistochemical staining equipment is shown in an embodiment of the utility model. Figure 3 As shown in the figure, the cleaning system 8 is located at the rear side of the equipment and is arranged behind the reagent assembly 401, the cleaning system 8 comprises a pump assembly 801, a valve assembly 802 and a pipeline assembly 803. The pump assembly 801 can provide conveying power for cleaning liquid, gas or waste liquid, so as to ensure that the liquid or gas can reach the target position at a set pressure. The multi-pass switching is realized through the valve assembly 802, that is, the flow path of the liquid or gas is controlled through the electromagnetic valve or the pneumatic valve, for example: the passageway of the purified water bin 703, the cleaning liquid bin 702 or the waste liquid bin 701 in the cleaning system 8 is switched through the valve assembly 802; the liquid path is switched into the gas path in the liquid spraying stage through the valve assembly 802 in the movable nozzle 5. The pipeline assembly 803 can realize efficient transmission of the liquid and the gas and reduce the pressure loss.

[0039] Figure 4 The structure schematic view of the reagent washing and mixing module is shown in an embodiment of the utility model. Figure 4 As shown in the figure, the reagent washing and mixing module 4 comprises a reagent assembly 401, a mixing station 402, a cleaning pool 403 and a support frame 10. Among them, the reagent assembly 401 is arranged at the front side of the support frame 10, and a group of mixing stations 402 and cleaning pools 403 are arranged on the left and right sides of the support frame 10. The reagent assembly 401, the mixing station 402 and the cleaning pool 403 in the reagent washing and mixing module 4 realize the precise management, efficient mixing and pollution prevention and control of the reagent through the functional division and collaborative control.

[0040] In specific embodiments, a plurality of independent cabins are built-in in the reagent assembly 401, and the reagents required for immunohistochemical staining are stored in categories, for example: the low-temperature bin at 4-8 DEG C is used to store the antibody and maintain the biological activity; the light-proof bin is used to store the light-sensitive reagent such as DAB and Fast Red; the normal-temperature bin is used to store the general cleaning liquid such as PBS and TBS. The mixing station 402 mixes different reagents according to the proportion and realizes homogenization in the way of vortex oscillation or micro-fluidic mixing. The cleaning pool 403 performs distributed cleaning on the steel needle 9: the high-pressure purified water in the purified water bin 703 is used to flush the surface residual reagent for pre-cleaning; the cleaning liquid in the cleaning liquid bin 702 is used for cleaning; the purified water in the purified water bin 703 is used for flushing again; the movable nozzle 5 is used to spray high-pressure gas to dry the steel needle 9. The waste liquid is filtered through the filter screen and then enters the waste liquid bin 701.

[0041] Figure 5 The schematic view of the container bin module is shown in an embodiment of the utility model. Figure 5As shown, the container warehouse module 7 includes a waste liquid warehouse 701, a cleaning liquid warehouse 702, and a purified water warehouse 703, and the waste liquid warehouse 702, the cleaning liquid warehouse 702, and the purified water warehouse 703 are arranged side by side from left to right. In a specific example, the cleaning system 8 first calls purified water from the purified water warehouse 703 to flush; then the cleaning system 8 switches to the cleaning liquid warehouse 702 to call cleaning liquid to clean; the cleaning system 8 then calls purified water in the purified water warehouse 703 for rinsing; finally, all waste liquid is filtered and collected into the waste liquid warehouse 701, and part of it can be recycled after classification and filtration.

[0042] In a specific embodiment, the operation steps of the utility model are as follows:

[0043] Step 1: Load the slide through the control module 1, the slide staining device 6 automatically moves to the outside of the equipment, and the slide is loaded by manual loading, and then the staining is started;

[0044] Step 2: Under the control of the control module 1, the slide staining device 6 moves back to the initial position, the movable nozzle 5 moves to above the slide loaded by the slide staining device 6 in the X-axis direction, then the cleaning system 8 draws the cleaning liquid in the cleaning liquid warehouse 702, sprays it on the slide through the liquid port of the movable nozzle 5, and stops spraying;

[0045] Step 3: Under the control of the control module 1, the cleaning system 8 sucks air and sprays it through the air port of the movable nozzle 5, and at the same time, the slide staining device 6 moves at a constant speed in the negative direction of the Y-axis, which is beneficial to dry the excess liquid on the slide, then the slide staining device 6 moves back to the initial position, and the air blowing stops;

[0046] Step 4: Under the control of the control module 1, the left or right pipette arm 3 moves above the reagent assembly 401, the built-in steel needle 9 draws the required reagent, then the steel needle 9 moves above the slide staining device 6, and the drawn reagent is dropped on the slide for a period of reaction;

[0047] Step 5: After the dropping is completed, the steel needle 9 moves to the inside of the cleaning pool 403, the cleaning system 8 is started, the steel needle 9 is cleaned at the same time, then the steel needle 9 is reset to the original point and waits for the next step;

[0048] It can be understood that steps 1-5 are the first cycle, the dropped reagent is a blocking agent, and the frozen immunohistochemistry generally needs to drop one antibody, a secondary antibody, DAB, and hematoxylin reagent, but the operation steps are consistent with the above. After the hematoxylin reagent is completed, the slide staining device 6 automatically moves to the outside of the equipment, the slide is taken out by hand, the next step is performed through the control module 1, the slide staining device 6 moves back to the inside of the equipment, and the staining is completed.

[0049] It is clear that a person skilled in the art can make various modifications and changes to the embodiments of the present application without departing from the spirit and scope of the present application. In this way, the present application also aims to encompass these modifications and changes if they are within the scope of the claims of the present application and their equivalents. The word "comprising" does not exclude the presence of other elements or steps than those listed in a claim. The simple fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be considered as limiting the scope.

Claims

1. A fully automated frozen rapid immunohistochemical staining apparatus, characterized by, The device comprises a control module, a pipetting arm, a reagent mixing module, a movable nozzle, a container warehouse module, a slide staining device and a cleaning system, the pipetting arm is a three-dimensional pipetting arm with X, Y and Z axis three-dimensional movement function, the reagent mixing module comprises a reagent assembly, a mixing station and a cleaning pool, the container warehouse module comprises a waste liquid warehouse, a cleaning liquid warehouse and a purified water warehouse, the cleaning liquid warehouse and the purified water warehouse are connected to the cleaning system through pipelines, the cleaning system is further connected to the liquid port of the movable nozzle and the cleaning pool, and finally flows back to the waste liquid warehouse; the cleaning system is also connected to the gas port of the movable nozzle through a pipeline, and the control module controls the slide staining device to move into or out of the equipment. The pipetting arm comprises a left pipetting arm and a right pipetting arm arranged symmetrically, and the left pipetting arm and the right pipetting arm independently operate.

2. The fully automated frozen rapid immunohistochemical staining device according to claim 1, characterized in that, The slide staining device is a plurality of independent channels, and a plurality of slides are simultaneously loaded.

3. The fully automated frozen rapid immunohistochemical staining device according to claim 1, wherein, The slide staining device is arranged in 8 groups, and each group corresponds to an independent channel.

4. The fully automated frozen rapid immunohistochemical staining device according to claim 3, characterized in that, The control module also controls the movement of the pipetting arm and the movable nozzle.

5. The fully automated frozen rapid immunohistochemical staining device according to claim 1, wherein, The control module controls the movable nozzle to move above the slide of the slide staining device in the X-axis direction, and the cleaning system draws cleaning liquid in the cleaning liquid warehouse and sprays it out through the liquid port of the movable nozzle.

6. The fully automated frozen rapid immunohistochemical staining device according to claim 5, characterized in that, When the gas port of the movable nozzle blows, the control module controls the slide staining device to move in the negative direction of the Y-axis.

7. The fully automated frozen rapid immunohistochemical staining device according to claim 5, characterized in that, The pipetting arm is provided with a steel needle, which is used to suck reagents in the reagent assembly.

8. The fully automated frozen rapid immunohistochemical staining device according to claim 4, characterized in that, In the working state, the control module controls the pipetting arm to move above the reagent assembly, the steel needle draws reagents in the reagent assembly, and moves above the slide staining device.

9. The fully automated frozen rapid immunohistochemical staining device according to claim 8, characterized in that, When the working state is separated, the steel needle moves to the inside of the cleaning pool, the cleaning system is started, and the steel needle is reset to the original point.

10. The fully automated frozen rapid immunohistochemical staining apparatus according to claim 9, wherein ​

Images